The proposed research seeks to generate fundamental information concerning in vitro surface properties of major pulmonary surfactant components, and then directly to use this information to formulate effective aerosol therapy for in vivo states of surfactant insufficiency. Specifically, in vitro experiments of dynamic surface pressure-area (pi-Xi) will be done with a modified Wilhelmy surface balance. In addition, studies of the adsorption of surfactants to the air-water interface, and Differential Scanning Calorimetry (DSC) determinations of gel to liquid crystal transition temperature (Tc) will also be performed. These in vitro surface property and DSC measurements will be used to suggest, a priori, specific component mixtures most likely to be effective as replacement therapy for in vivo states of lung surfactant insufficiency on the basis of their high maximal surface pressure, good surface adsorption properties, and significant respreading after dynamic compression past monolayer collapse. The most promising component mixtures will be delivered in aerosol form to the lungs of living animals as well as to excised lungs. The distribution of intra-pulmonary deposition will be determined, and the effect of the administered aerosol on lung compliance will be assessed by evaluating standard pressure-volume characteristics of lungs with and without the aerosolized material. Microscopy will be used to look for any cellular or sub-cellular reaction to the aerosolized phospholipid solution in the lung.